Supramolecular Platform Stabilizing Growth Factors

High concentrations of supplemented growth factors can cause oversaturation and adverse effects in <i>in vitro</i> and <i>in vivo</i> studies, though these supraphysiological concentrations are often required due to the low stability of growth factors. Here we demonstrate the stabilization of TGF-β1 and BMP4 using supramolecular polymers. Inspired by heparan sulfate, sulfonated peptides were presented on a supramolecular polymer to allow for noncovalent binding to growth factors in solution. After mixing with excipient molecules, both TGF-β1 and BMP4 were shown to have a prolonged half-life compared to the growth factors free in solution. Moreover, high cellular response was measured by a luciferase assay, indicating that TGF-β1 remained highly active upon binding to the supramolecular assembly. The results demonstrate that significant lower concentrations of growth factors can be used when supramolecular polymers bearing growth factor binding moieties are implemented. This approach can also be exploited in hydrogel systems to control growth factor release

Pathway Selection in Peptide Amphiphile Assembly

The nature of supramolecular structures could be strongly affected by the pathways followed during their formation just as mechanisms and final outcomes in chemical reactions vary with the conditions selected. So far this is a largely unexplored area of supramolecular chemistry. We demonstrate here how different preparation protocols to self-assemble peptide amphiphiles in water can result in the formation of different supramolecular morphologies, either long filaments containing β-sheets or smaller aggregrates containing peptide segments in random coil conformation. We found that the assembly rate into β-sheets decreases in the presence of a destabilizing “good” solvent like hexafluoroisopropanol (HFIP) and is affected by transient conditions in solution. Also the peptide amphiphile investigated spontaneously nucleates the β-sheet-containing filaments at a critical fraction of HFIP in water below 21%. Furthermore, β-sheet assemblies have a high kinetic stability and, once formed, do not disassemble rapidly. We foresee that insights into the characteristic dynamics of a supramolecular system provide an efficient approach to select the optimum assembly pathway necessary for function

Amplifying Chiroptical Properties of Conjugated Polymer Thin-Film Using an Achiral Additive

Chiral conjugated polymers bearing enantiopure side chains offer the possibility to harness the effect of chirality in organic electronic devices. However, its use is hampered by the low degree of circular polarization in absorption (<i>g</i>_abs) in most of the conjugated polymer thin-films studied. Here we demonstrate a versatile method to significantly increase the <i>g</i>_abs by using a few weight percentages of a commercially available achiral long-chain alcohol as an additive. This additive enhances the chiroptical properties in both absorption and emission by ca. 5–10 times in the thin-films. We envisage that the alcohol additive acts as a plasticizer which enhances the long-range chiral liquid crystalline ordering of the polymer chains, thereby amplifying the chiroptical properties in the thin-film. The application of this methodology to various conjugated polymers has been demonstrated

From Molecular Structure to Macromolecular Organization: Keys to Design Supramolecular Biomaterials

In the past decade, significant progress has been made in the field of biomaterials, for potential applications in tissue engineering or drug delivery. We have recently developed a new class of thermoplastic elastomers, based on ureidopyrimidinone (UPy) quadruple hydrogen bonding motifs. These supramolecular polymers form nanofiber-like aggregates initially <i>via</i> the dimerization of the UPy units followed by lateral urea-hydrogen bonding. Combined kinetic and thermodynamic studies unravel the pathway complexity in the formation of these polymorphic nanofibers and the subtlety of the polymer’s design, while these morphologies are so critically important when these materials are used in combination with cells. We also show that the cell behavior directly depends on the length and shape of the nanofibers, illustrating the key importance of macromolecular and supramolecular organization of biomaterials. This study leads to new design rules that determine what factors are decisive for a polymer to be a good candidate as biomaterial

Self-Assembly of Hydrogen-Bonding Gradient Copolymers: Sequence Control via Tandem Living Radical Polymerization with Transesterification

Chiral 1,3,5-tricarboxamide (BTA)-functionalized copolymers with gradient, bidirectional gradient, and random sequence distributions were synthesized via tandem living radical polymerization (LRP) with in situ monomer transesterification to investigate the effects of the BTA sequence on self-folding/aggregation properties in organic media. Here, 2-ethylhexyl methacrylate (EHMA) as a starting monomer was polymerized with a ruthenium catalytic system in the presence of a chiral BTA-bearing alcohol (BTA-OH) and Ti­(O<i>i</i>-Pr)₄. By tuning the concentration and time of addition of the Ti catalyst, the transesterification rate of EHMA into a chiral BTA-functionalized methacrylate (BTAMA) was synchronized with LRP to produce EHMA/BTAMA gradient or bidirectional gradient copolymers. In contrast, faster transesterification than LRP gave the corresponding random copolymer. Circular dichroism spectroscopy and dynamic light scattering performed on solutions of all BTA-functionalized copolymers indicated that the chiral BTA pendants self-assemble helically via hydrogen-bonding interaction in 1,2-dichloroethane, methyl­cyclohexane (MCH), and their mixtures to form single-chain or multichain polymeric nanoparticles. The temperature-dependent self-assembly behavior of the BTA pendants was virtually independent of the sequence distribution, whereas the size of the resultant nanoparticles depended on the sequence as follows: random < gradient < bidirectional gradient in MCH

Sticky Supramolecular Grafts Stretch Single Polymer Chains

The folding of single polymeric chains into single chain polymeric nanoparticles (SCPNs) is a unique strategy to prepare ordered structures at the nanoscopic level. Structure forming elements are attached to a polymer chain designed to fold it into a well-defined object, the SCPN. The self-assembly of these units has been investigated in great detail. However, little is known about the impact of the resulting secondary structure on the conformation of the polymer chain. Here we employ a combination of scattering methods and spectroscopy to study how pendant chiral benzene-1,3,5-tricarboxamides (BTAs) fold oligo­(ethylene glycol) methyl ether methacrylate-based polymers into SCPNs. Circular dichroism spectroscopy shows that the extent of BTA self-assembly on the polymer chain in water can be fine-tuned by means of temperature and cosolvent addition (isopropanol). Small-angle neutron scattering experiments demonstrate that single polymer chains have an asymmetric shape with a constant cross section, <i>R</i>_cs, and variable length, <i>L</i>, with <i>L</i> > <i>R</i>_cs. The polymer chain extends and shortens in response to variations in temperature and solvent composition, which also influence the self-assembly of the BTA units. The SCPNs stretch upon association and shrink upon disassociation of the grafted supramolecular moieties

Branched Block Copolymers for Tuning of Morphology and Feature Size in Thin Film Nanolithography

A library of Y-shaped poly­(dimethylsiloxane) (PDMS)-<i>b</i>-poly­(d,l-lactide) (PLA) diblock copolymers and their corresponding linear counterparts were synthesized, and their morphologies and feature sizes in bulk and thin films were compared using small-angle X-ray scattering (SAXS), scanning force microscopy (SFM), and grazing incidence small-angle X-ray scattering (GI-SAXS). For macromolecular isomers with approximately the same molecular weights and volume fractions (PLA <i>f</i>_L: 0.20 and 0.35), different thin film morphologies were obtained for the Y-shaped PDMS-<i>b</i>-PLA derivatives when compared to the corresponding linear derivatives. These data also gave us the option to determine some of the key parameters of these block copolymers. A relatively high χ value of 0.24 was found for these PDMS-<i>b</i>-PLA systems and was shown to be influenced by architecture

Tough Stimuli-Responsive Supramolecular Hydrogels with Hydrogen-Bonding Network Junctions

Hydrogels were prepared with physical cross-links comprising 2-ureido-4­[1H]-pyrimidinone (UPy) hydrogen-bonding units within the backbone of segmented amphiphilic macromolecules having hydrophilic poly­(ethylene glycol) (PEG). The bulk materials adopt nanoscopic physical cross-links composed of UPy–UPy dimers embedded in segregated hydrophobic domains dispersed within the PEG matrix as comfirmed by cryo-electron microscopy. The amphiphilic network was swollen with high weight fractions of water (<i>w</i>_H₂O ≈ 0.8) owing to the high PEG weight fraction within the pristine polymers (<i>w</i>_PEG ≈ 0.9). Two different PEG chain lengths were investigated and illustrate the corresponding consequences of cross-link density on mechanical properties. The resulting hydrogels exhibited high strength and resilience upon deformation, consistent with a microphase separated network, in which the UPy–UPy interactions were adequately shielded within hydrophobic nanoscale pockets that maintain the network despite extensive water content. The cumulative result is a series of tough hydrogels with tunable mechanical properties and tractable synthetic preparation and processing. Furthermore, the melting transition of PEG in the dry polymer was shown to be an effective stimulus for shape memory behavior

Nanostructured Supramolecular Block Copolymers Based on Polydimethylsiloxane and Polylactide

Hierarchical self-assembly has been demonstrated with diblock copolymers comprising poly­(dimethylsiloxane) (PDMS) and poly­(lactide) (PLA) with supramolecular, 4-fold hydrogen-bonding junctions. PDMS with a single ureidoguanosine unit at the end was synthesized by a postpolymerization strategy. PLA with a single 1,7-diamidonaphthyridine was synthesized by ring-opening polymerization from the appropriate functional initiator. Selective association of the end groups to form distinct, noncovalent connections between the respective homopolymers in blends was established by ¹H NMR spectroscopy. The orthogonal self-assembly of the resulting pseudoblock copolymer, driven by immiscibility between the polymer constituents was demonstrated. Bulk polymer blends were prepared that have approximately symmetric composition and a 1:1 end-group stoichiometry. Small angle X-ray scattering combined with differential scanning calorimetry and transmission electron microscopy provide unambiguous evidence for the adoption of a lamellar morphology having long-range order, nanoscopic domain dimensions (20 nm pitch), and a sharp domain interface defined by the supramolecular building blocks

Modular Synthetic Platform for the Construction of Functional Single-Chain Polymeric Nanoparticles: From Aqueous Catalysis to Photosensitization

Single-chain polymeric nanoparticles (SCPNs) are intriguing systems for multiple applications. In order to arrive at a controlled, but random, positioning of the different side groups to the polymer backbone, alternative synthetic routes have to be developed. Here, a general postpolymerization modification strategy of poly­(pentafluorophenyl acrylate) (pPFPA) is presented as a versatile method to rapidly access functional SCPNs. We first show that the sequential addition of a benzene-1,3,5-tricarboxamide-based amine, acting as the supramolecular recognition motif, and water-soluble polyetheramine (Jeffamine) to pPFPA affords random copolymers that fold in water into SCPNs. The scope of the modular platform is illustrated by preparing two types of functional SCPNs. First, we prepared SCPNs designed for bio-orthogonal catalysis by attaching pendant mono­(benzimidazoylmethyl)-bis­(pyridylmethyl) (Bimpy), phenanthroline (Phen), or 2,2′-bipyridine (BiPy), ligands capable of binding either Cu­(I) or Pd­(II). The Bimpy- and Phen-containing SCPNs ligated to Cu­(I) significantly accelerate azide–alkyne cycloaddition reactions while Bipy-containing SCPNs ligated to Pd­(II) efficiently catalyze depropargylation reactions. In all cases, reactions proceeded efficiently in phosphate buffer at a physiological pH and at low substrate concentrations. Next, the potential of SCPNs for photodynamic therapy was evaluated. Introducing porphyrins in SCPNs leads to novel photosensitizers that can produce singlet oxygen (¹O₂) upon photoirradiation. Additionally, by attaching both porphyrins and prodrug models, attached via ¹O₂-cleavable amino-acrylate linker, to the SCPNs, we show that irradiation of the SCPNs results in a cascade reaction of ¹O₂ generation followed by cleavage of the amino-acrylate linkers, releasing the drug model. The modular synthesis strategy reported here provides rapid and controlled access to SCPNs with tunable amounts of active units that fulfill different functions